HIV continues to spread among injecting drug users (IDUs) in many countries around the world. In recent years, cities in Eastern Europe, the Russian Federation, India, China, and other parts of Asia have experienced rapid increases in HIV prevalence among IDUs, while HIV prevalence has remained low and stable among IDUs in other cities despite high levels of injecting risk. Twenty-five years into the HIV epidemic among IDUs, researchers still do not really know why the virus spreads more in some places than others. Simple rates of syringe sharing and unprotected sex do not account for varying degrees of HIV transmission. One widely overlooked factor that could significantly contribute to these differences in HIV spread is the type of syringes that IDUs are using. The proposed study represents one step in the process of assessing the role of syringe type in HIV epidemics among IDUs. To date, we have established that it is biologically plausible that the type of syringe may play a role in HIV transmission by demonstrating that high dead-space syringes (HDSSs) retain over 1,000 times more blood after use and rinsing than low dead-space syringes (LDSSs) retain. We have linked a history of sharing HDSSs with prevalent HIV and HCV infection, and we have developed mathematical models that suggest injection-related HIV epidemics may not occur in cities, if fewer than 10% of IDUs are using HDSSs. The next step is to collect empirical data to test this finding. Large multisite longitudinal HIV incidence studies that collect data from individual IDUs on the types of syringes that they are using will be needed to establish a causal relationship between HDSSs and HIV infection among IDUs. However, these studies would require a considerable investment in time and money. Thus, we propose to conduct a small exploratory study to identify cities in Europe, Russia, and Asia where HIV prevalence among IDUs is high and cities where HIV prevalence among IDUs is low. We will seek to obtain information on the types of syringes that IDUs are using in these cities. The proposed study has the potential for yielding extremely valuable data for minimal investment. The specific aim of the proposed study is: To compare the types of syringes used by IDUs in cities where HIV prevalence among IDUs is high (>30%) or increasing (>5% per year for >3 years) with the types of syringes that IDUs are using in a matched comparison group of cities with low and stable HIV prevalence (<5% for >5 years). Should we find an ecological association between use of HDSSs and HIV prevalence, we will propose larger studies with the purpose of better delineating causal inference, including the role for sexual transmission. PUBLIC HEALTH RELEVANCE: The information obtained in this project may substantially increase our knowledge of HIV transmission among injecting drug users (IDUs). If we find that the types of syringes used by IDUs influence HIV transmission, this could lead to relatively straightforward interventions that could substantially reduce HIV transmission in this high risk group. This in turn could reduce sexual transmission of HIV from IDUs to the general population.